Real-world use of emicizumab in Chinese children with hemophilia A: Retrospective data from a comprehensive care center

Qianqian Mao; Zhenping Chen; Guoqing Liu; Gang Li; Yingzi Zhen; Xiaoling Cheng; Zekun Li; Wanru Yao; Di Ai; Zhengping Li; Nan Wang; Man-Chiu Poon; Runhui Wu

doi:10.1002/ped4.12439

Real-world use of emicizumab in Chinese children with hemophilia A: Retrospective data from a comprehensive care center

Pediatr Investig. 2024 Jul 22;8(4):244-252. doi: 10.1002/ped4.12439. eCollection 2024 Dec.

Authors

Qianqian Mao^{1

2}, Zhenping Chen², Guoqing Liu^{1

2}, Gang Li², Yingzi Zhen¹, Xiaoling Cheng³, Zekun Li¹, Wanru Yao¹, Di Ai^{1

2}, Zhengping Li^{1

2}, Nan Wang^{1

2}, Man-Chiu Poon⁴, Runhui Wu¹

Affiliations

¹ Hematology Department, Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, Key Laboratory of Major Diseases in Children, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Children's Hospital, Capital Medical University Beijing China.
² Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University Beijing China.
³ Department of Pharmacy Beijing Children's Hospital, Capital Medical University, National Center for Children's Health Beijing China.
⁴ Departments of Medicine, Foothills Medical Centre University of Calgary 1403-29th Street NW Calgary T2N 2T9 Alberta Canada.

Abstract

Importance: Emicizumab (EMI) is efficacious and safe for hemophilia A (HA) prophylaxis. However, its high cost poses a challenge in China.

Objective: To explore the possibility of using reduced-dosage EMI in Chinese HA children.

Methods: We conducted a retrospective study for HA children in our Comprehensive Care Center. Data were collected pre- and post-EMI treatment to evaluate bleeding rates. Laboratory analyses included factor VIII (FVIII)-like activity and EMI concentration measurements.

Results: Thirty-four HA children receiving EMI prophylaxis for a median (range) 24.5 (2.5-47.9) months by June 2023. Of these, 25 (73.5%) were under 3 years of age, 26 (76.5%) had severe hemophilia and 12 (35.3%) were minimally treated or previously untreated patients. Thirty-one (91.2%) of the 34 patients received reduced-dosage EMI for economic reasons. EMI concentration and FVIII-like activity measured showed a strong correlation. Overall, while on EMI, their annual treated bleeding rate (ATBR) and annual bleeding rate (ABR) decreased significantly (2-0) while their zero-bleeding rate (ZBR) increased significantly (11.5%-65.4%). After 6 months of EMI, there was no significant difference in ATBR and ABR among various maintenance dosages. However, ZBR was significantly lower in dosages under 4 mg/kg (P = 0.0156). Receiver operator characteristic curves suggested the following cutoff values for zero bleeding: EMI 4-weekly maintenance dosage 3.8 mg/kg, EMI concentration 48.1 μg/mL, and FVIII-like activity 15.4 IU/dL.

Interpretation: We showed EMI effectively prevented bleeding even at reduced dosages. However, the bleeding risk may be higher with EMI 4-weekly maintenance dosage <3.8 mg/kg, EMI concentration <48.1 μg/mL, and FVIII-like activity <15.4 IU/dL for zero bleeding. It is important that dosage reduction be done rationally. Dosage tailoring is possible.

Keywords: Emicizumab; Hemophilia A; Prophylaxis.